Amyloid formation by the pro-inflammatory S100A8/A9 proteins in the ageing prostate

Kiran Yanamandra, Oleg Alexeyev, Vladimir Zamotin, Vaibhav Srivastava, Andrei Shchukarev, Ann Christin Brorsson, Gian Gaetano Tartaglia, Thomas Vogl, Rakez Kayed, Gunnar Wingsle, Jan Olsson, Christopher M. Dobson, Anders Bergh, Fredrik Elgh, Ludmilla A. Morozova-Roche

Research output: Contribution to journalArticle

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Abstract

Background: The conversion of soluble peptides and proteins into polymeric amyloid structures is a hallmark of many age-related degenerative disorders, including Alzheimer's disease, type II diabetes and a variety of systemic amyloidoses. We report here that amyloid formation is linked to another major age-related phenomenon - prostate tissue remodelling in middle-aged and elderly men. Methodology/Principal Findings: By using multidisciplinary analysis of corpora amylacea inclusions in prostate glands of patients diagnosed with prostate cancer we have revealed that their major components are the amyloid forms of S100A8 and S100A9 proteins associated with numerous inflammatory conditions and types of cancer. In prostate protease rich environment the amyloids are stabilized by dystrophic calcification and lateral thickening. We have demonstrated that material closely resembling CA can be produced from S100A8/A9 in vitro under native and acidic conditions and shows the characters of amyloids. This process is facilitated by calcium or zinc, both of which are abundant in ex vivo inclusions. These observations were supported by computational analysis of the S100A8/A9 calcium-dependent aggregation propensity profiles. We found DNA and proteins from Escherichia coli in CA bodies, suggesting that their formation is likely to be associated with bacterial infection. CA inclusions were also accompanied by the activation of macrophages and by an increase in the concentration of S100A8/A9 in the surrounding tissues, indicating inflammatory reactions. Conclusions/Significance: These findings, taken together, suggest a link between bacterial infection, inflammation and amyloid deposition of pro-inflammatory proteins S100A8/A9 in the prostate gland, such that a self-perpetuating cycle can be triggered and may increase the risk of malignancy in the ageing prostate. The results provide strong support for the prediction that the generic ability of polypeptide chains to convert into amyloids could lead to their involvement in an increasing number of otherwise apparently unrelated diseases, particularly those associated with ageing.

Original languageEnglish (US)
Article numbere5562
JournalPLoS One
Volume4
Issue number5
DOIs
StatePublished - May 15 2009

Fingerprint

Calgranulin A
amyloid
Amyloid
Prostate
Aging of materials
Proteins
proteins
prostate gland
bacterial infections
Bacterial Infections
Calgranulin B
middle-aged adults
Tissue
Calcium
calcium
macrophage activation
amyloidosis
Peptides
Macrophage Activation
Macrophages

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Yanamandra, K., Alexeyev, O., Zamotin, V., Srivastava, V., Shchukarev, A., Brorsson, A. C., ... Morozova-Roche, L. A. (2009). Amyloid formation by the pro-inflammatory S100A8/A9 proteins in the ageing prostate. PLoS One, 4(5), [e5562]. https://doi.org/10.1371/journal.pone.0005562

Amyloid formation by the pro-inflammatory S100A8/A9 proteins in the ageing prostate. / Yanamandra, Kiran; Alexeyev, Oleg; Zamotin, Vladimir; Srivastava, Vaibhav; Shchukarev, Andrei; Brorsson, Ann Christin; Tartaglia, Gian Gaetano; Vogl, Thomas; Kayed, Rakez; Wingsle, Gunnar; Olsson, Jan; Dobson, Christopher M.; Bergh, Anders; Elgh, Fredrik; Morozova-Roche, Ludmilla A.

In: PLoS One, Vol. 4, No. 5, e5562, 15.05.2009.

Research output: Contribution to journalArticle

Yanamandra, K, Alexeyev, O, Zamotin, V, Srivastava, V, Shchukarev, A, Brorsson, AC, Tartaglia, GG, Vogl, T, Kayed, R, Wingsle, G, Olsson, J, Dobson, CM, Bergh, A, Elgh, F & Morozova-Roche, LA 2009, 'Amyloid formation by the pro-inflammatory S100A8/A9 proteins in the ageing prostate', PLoS One, vol. 4, no. 5, e5562. https://doi.org/10.1371/journal.pone.0005562
Yanamandra K, Alexeyev O, Zamotin V, Srivastava V, Shchukarev A, Brorsson AC et al. Amyloid formation by the pro-inflammatory S100A8/A9 proteins in the ageing prostate. PLoS One. 2009 May 15;4(5). e5562. https://doi.org/10.1371/journal.pone.0005562
Yanamandra, Kiran ; Alexeyev, Oleg ; Zamotin, Vladimir ; Srivastava, Vaibhav ; Shchukarev, Andrei ; Brorsson, Ann Christin ; Tartaglia, Gian Gaetano ; Vogl, Thomas ; Kayed, Rakez ; Wingsle, Gunnar ; Olsson, Jan ; Dobson, Christopher M. ; Bergh, Anders ; Elgh, Fredrik ; Morozova-Roche, Ludmilla A. / Amyloid formation by the pro-inflammatory S100A8/A9 proteins in the ageing prostate. In: PLoS One. 2009 ; Vol. 4, No. 5.
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